Insulin-like growth factor

IGF1/GH Axis

The IGF "axis" is also commonly referred to as the Growth Hormone/IGF1 Axis. IGF-I expression is required for achieving maximal growth. Gene knockout studies in mice have confirmed this, though other animals are likely to regulate the expression of these genes in distinct ways. While IGF-2 may be primarily fetal in action it is also essential for development and function of organs such as the brain, liver and kidney.

Factors that are known to cause variation in the levels of GH and IGF-1 in the circulation include an individuals genetic make-up, the time of day, their age, sex, exercise status, stress levels, genetics, nutrition level and body mass index (BMI), disease state, race, estrogen status and xenobiotic intake. The later inclusion of xenobiotic intake as a factor influencing GH-IGF status highlights the fact that the GH-IGF axis is a potential target for certain endocrine disrupting chemicals - see also endocrine disruptor.

IGF Targets

Almost every cell in the human body is affected by DNA synthesis.

IGF-2 is secreted by the brain, kidney, IGF-1. In adult humans it is found at 600 times the concentration of insulin.^{[citation needed]}

IGF Receptors

Further work is required to determine the main receptor tyrosine kinase - meaning the receptor signals by causing the addition of a phosphate molecule on particular tyrosines. The IGF-2 receptor only binds IGF-2 and acts as a "clearance receptor" - it activates no intracellular signalling pathways, functioning only as an IGF-2 sequestering agent and preventing IGF-2 signalling.

IGF Binding Proteins

IGF-1 and IGF-2 are regulated by a family of proteins known as the IGF-Binding Proteins. These proteins help to modulate IGF action in complex ways that involve both inhibiting IGF action by preventing binding to the IGF-1 receptor as well as promoting IGF action possibly through aiding in delivery to the receptor and increasing IGF half-life. Currently, there are 6 characterized IGF Binding Proteins (IGFBP1-6). There is currently significant data suggesting that IGFBPs play important roles in addition to their ability to regulate IGFs.

Diseases affected by IGF

Studies of recent interest show that the Insulin/IGF axis play an important role in aging². insulin, IGFs, relaxins, EPIL, and relaxin-like factor)^{[citation needed]} and have apparently distinct roles with some but relatively less crosstalk. On the other hand, lower organisms typically have fewer receptors (only 1 known in the nematode)^[2], and the roles of these other insulins are unknown. Furthermore lower animals do not have specialized organs (islets of Langerhans) which sense insulin in response to glucose homeostasis. Therefore it is an open question as to whether either IGF1 or insulin in the mammal may perturb aging, although there is strong suggestion dietary restriction phenomena are related.

Other studies are beginning to uncover the important role the IGFs play in diseases such as cancer and diabetes, showing for instance that IGF-1 stimulates growth of both prostate and breast cancer cells. Researchers are not in complete agreement about the degree of cancer risk that IGF-1 poses.

See also

• Insulin-like growth factor 1
• Insulin-like growth factor 2
• Growth hormone treatment
• HGH controversies

References

1. Cohen, Pinchas, et al. "Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins in primary cultures of prostate epithelial". Journal of Clinical Endocrinology and Metabolism, Vol. 73, No. 2, 1991, pp. 401-07
2. F. Yaghmaie, O. Saeed, S.A. Garan, M.A. Voelker, A.M. Gouw, W. Freitag, H. Sternberg and P.S. Timiras "Age-dependent loss of insulin-like growth factor-1 receptor immunoreactive cells in the supraoptic hypothalamus is reduced in calorically restricted mice". International Journal of Developmental Neuroscience, Vol. 24, Issue 7, 2006, pp. 431-436
3. Lippman, Marc E. "The development of biological therapies for breast cancer". Science, Vol. 259, January 29 1993, pp. 631-32
4. Papa, Vincenzo, et al. "Insulin-like growth factor-I receptors are overexpressed and predict a low risk in human breast cancer". Cancer Research, Vol. 53, 1993, pp. 3736-40
5. Scarth, J "Modulation of the Growth Hormone-Insulin-Like Growth Factor (GH-IGF) axis by pharmaceutical, nutraceutical and environmental xenobiotics: an emerging role for xenobiotic metabolizing enzymes and the transcription factors regulating their expression. A review.". Xenobiotica, Vol. 36, (2-3) pp. 119-218
6. Woods, Alisa G. "Deafferentation-induced increases in hippocampal insulin-like growth factor-1 messenger RNA expression are severely attenuated in middle aged and aged rats." Neuroscience, Vol. 83, (3) pp. 663-668